In silico approach to screen compounds active against parasitic nematodes of major socio-economic importance

Infections due to parasitic nematodes are common causes of morbidity and fatality around the world especially in developing nations. At present however, there are only three major classes of drugs for treating human nematode infections. Additionally the scientific knowledge on the mechanism of action and the reason for the resistance to these drugs is poorly understood. Commercial incentives to design drugs that are endemic to developing countries are limited therefore, virtual screening in academic settings can play a vital role is discovering novel drugs useful against neglected diseases. In this study we propose to build robust machine learning model to classify and screen compounds active against parasitic nematodes.A set of compounds active against parasitic nematodes were collated from various literature sources including PubChem while the inactive set was derived from DrugBank database. The support vector machine (SVM) algorithm was used for model development, and stratified ten-fold cross validation was used to evaluate the performance of each classifier. The best results were obtained using the radial basis function kernel. The SVM method achieved an accuracy of 81.79% on an independent test set. Using the model developed above, we were able to indentify novel compounds with potential anthelmintic activity.In this study, we successfully present the SVM approach for predicting compounds active against parasitic nematodes which suggests the effectiveness of computational approaches for antiparasitic drug discovery. Although, the accuracy obtained is lower than the previously reported in a similar study but we believe that our model is more robust because we intentionally employed stringent criteria to select inactive dataset thus making it difficult for the model to classify compounds. The method presents an alternative approach to the existing traditional methods and may be useful for predicting hitherto novel anthelmintic compounds.12 page(s

Constraints on low-mass, relic dark matter candidates from a surface-operated SuperCDMS single-charge sensitive detector

This article presents an analysis and the resulting limits on light dark matter inelastically scattering off of electrons, and on dark photon and axionlike particle absorption, using a second-generation SuperCDMS high-voltage eV-resolution detector. The 0.93 g Si detector achieved a 3 eV phonon energy resolution; for a detector bias of 100 V, this corresponds to a charge resolution of 3% of a single electron-hole pair. The energy spectrum is reported from a blind analysis with 1.2 g-days of exposure acquired in an above-ground laboratory. With charge carrier trapping and impact ionization effects incorporated into the dark matter signal models, the dark matter-electron cross section σ_e is constrained for dark matter masses from 0.5 to 10⁴  MeV/c²; in the mass range from 1.2 to 50  eV/c² the dark photon kinetic mixing parameter ϵ and the axioelectric coupling constant gae are constrained. The minimum 90% confidence-level upper limits within the above-mentioned mass ranges are σ_e = 8.7×10⁻³⁴ cm², ϵ = 3.3×10⁻¹⁴, and g_(ae) = 1.0×10⁻⁹

Ionization yield measurement in a germanium CDMSlite detector using photo-neutron sources

Two photo-neutron sources, $^{88}$Y$^{9}$Be and $^{124}$Sb$^{9}$Be, have been used to investigate the ionization yield of nuclear recoils in the CDMSlite germanium detectors by the SuperCDMS collaboration. This work evaluates the yield for nuclear recoil energies between 1 keV and 7 keV at a temperature of $\sim$ 50 mK. We use a Geant4 simulation to model the neutron spectrum assuming a charge yield model that is a generalization of the standard Lindhard model and consists of two energy dependent parameters. We perform a likelihood analysis using the simulated neutron spectrum, modeled background, and experimental data to obtain the best fit values of the yield model. The ionization yield between recoil energies of 1 keV and 7 keV is shown to be significantly lower than predicted by the standard Lindhard model for germanium. There is a general lack of agreement among different experiments using a variety of techniques studying the low-energy range of the nuclear recoil yield, which is most critical for interpretation of direct dark matter searches. This suggests complexity in the physical process that many direct detection experiments use to model their primary signal detection mechanism and highlights the need for further studies to clarify underlying systematic effects that have not been well understood up to this point

Search for low-mass dark matter via bremsstrahlung radiation and the Migdal effect in SuperCDMS

We present a new analysis of previously published SuperCDMS data using a profile likelihood framework to search for sub-GeV dark matter (DM) particles through two inelastic scattering channels: bremsstrahlung radiation and the Migdal effect. By considering these possible inelastic scattering channels, experimental sensitivity can be extended to DM masses that are undetectable through the DM-nucleon elastic scattering channel, given the energy threshold of current experiments. We exclude DM masses down to 220  MeV/c2 at 2.7×10−30  cm2 via the bremsstrahlung channel. The Migdal channel search provides overall considerably more stringent limits and excludes DM masses down to 30  MeV/c2 at 5.0×10−30  cm2

A Search for Low-mass Dark Matter via Bremsstrahlung Radiation and the Migdal Effect in SuperCDMS

We present a new analysis of previously published of SuperCDMS data using a profile likelihood framework to search for sub-GeV dark matter (DM) particles through two inelastic scattering channels: bremsstrahlung radiation and the Migdal effect. By considering these possible inelastic scattering channels, experimental sensitivity can be extended to DM masses that are undetectable through the DM-nucleon elastic scattering channel, given the energy threshold of current experiments. We exclude DM masses down to $220~\textrm{MeV}/c^2$ at $2.7 \times 10^{-30}~\textrm{cm}^2$ via the bremsstrahlung channel. The Migdal channel search provides overall considerably more stringent limits and excludes DM masses down to $30~\textrm{MeV}/c^2$ at $5.0 \times 10^{-30}~\textrm{cm}^2$.Comment: Submitted to PR